3 - Pharmacokinetics Flashcards
Define pharmacokinetics
- What the body does with the drug
- Movement of the drug within the body
Define pharmacodynamics
- What drug does to the body
- Body’s response to the drug
What are the factors that allow drugs to work?
- Must be in the right place
- Must be at the right concentration
- Must be in body for the right amount of time
- Has to be the correct dose
What makes a dosage the correct dose?
There are no undesired or dangerous side effects
What is ADME?
Absorption, distribution, metabolism, elimination
What is the difference between absorption and adsorption?
Absorption - transfer into another substance
Adsorption - transfer onto another substance (on the surface)
Under what circumstances does absorption occur in the a) gut wall, b) blood and c) oral mucosa?
a) Extravascular administration (e.g. oral)
b) Intravascular administration
c) Buccal administration
Where does ADME occur?
A - Gut wall and blood
D - Body tissues
M - Liver
E - Kidneys
How is the drug transported in the blood?
- Filtration through pores
- Passive diffusion (pass through membrane, no ATP)
- Active transport (pass through ion channels, ATP)
- Facilitated diffusion (pass through ion channels, no ATP)
- Phagocytosis - cells ‘eat’ drug
- Pinocytosis - cells ‘drink’ drug
What happens during oral administration? E.g. swallowing a tablet
- Drug dissolved in gastric juices
- Drug mainly absorbed in small intestine, diffuse into hepatic portal vein
- Drug acidic? Unionised & absorbed in stomach & small intestines
- Drug basic? Travel to liver via hepatic portal system
- Drugs metabolised in liver -> sent to right side of heart -> lungs -> left side of heart -> enters circulatory system
What happens during inhalation administration? E.g. smoking
Drug enters lungs -> diffuses into blood stream from alveoli -> enters left side of heart -> enters circulatory system
What happens during intravenous administration? E.g. injecting
Drug enters circulatory system immediately
What happens during transdermal administration? E.g. patch
Drug diffuses into skin -> diffuses into blood & enters circulatory system
Define bioavailability
How much of the drug reaches systemic circulation
Define first pass metabolism/effect
How much drug is metabolised before reaching systemic circulation
Explanation:
all drug absorbed in GI tract -? goes to liver via hepatic portal vein -> some drug metabolised
What are the factors affecting distribution?
Main:
- Chemical structure of drug
- Route of administration
- Presence of food in GI tract
- Rate of blood flow
Additional:
- Membrane permeability
- Blood perfusion (passage from blood to organs/tissues)
- Lipid solubility (high water solubility means cross blood/brain barrier faster, high lipid solubility causes drugs to be stored in fats so higher dosage needed. More fat on a person = higher dosage of drug)
- Plasma protein
- Intracellular binding
- pH
Where and how does metabolism take place?
Liver, broken down by P450 enzymes
Define metabolism and its purpose
- Biochemical modification/degradation of a drug through enzymatic action
- Make a drug more polar to allow for easy and quick elimination (urine)
- Production of metabolites
What is phase 1 metabolism? List the processes
- Non-synthetic reactions. Result in active/inactive drug
- Hydrolysis e.g. cocaine
- Oxidation e.g. atropine
- Reduction e.g. flunitrazepam
- Dealkylation e.g. codeine
- Deacetylation e.g. heroin
What is phase 2 metabolism? List the processes
- Synthetic reactions or conjugation. Usually results in inactive drug, but an exception is morphine-6-conjugate (active metabolite of morphine)
- Sulphation (+ sulphur group, makes water soluble)
- Glucuronidation (+ glucuronic acid, make water soluble)
- Acetylation (+ acetyl group)
- Amino acid conjugation (+ amino acid, make water soluble)
Name the different ways drugs are eliminated from the body
Air (expiration) - pulmonary
Faeces - bile (lipid-soluble substances)
Urine - renal (water-soluble substances)
Most drugs metabolised to water soluble substances
What is the hepatic portal system?
- Network of capillaries that carry blood from capillaries in stomach, intestine, spleen and pancreas to those in the liver
- Filtration system
- Deliver deoxygenated blood to liver to be detoxified before going to heart
What is the Cmax and tmax
Cmax - maximum concentration of drug
tmax - time of maximum concentration
What is the equation for volume of distribution?
= total amount of drug present/concentration of blood plasma
What is half-life (t1/2)?
Time it takes for the drug plasma concentration to halve
What is ED50?
Concentration of drug that produces the desired therapeutic effect in 50% of the population
What is TD50?
Concentration of drug which produces a toxic effect in 50% of the population
What is the equation for blood alcohol concentration?
= total alcohol consumed-amount of alcohol metabolised/volume of distribution
Name the analytical techniques involved in urine drug testing?
- Colour test
- Immunoassays
- TLC
- GLC
- GC/MS
- GC/IR